Recent pilot trials have demonstrated the safety of transplanting HCV-viremic kidneys into HCV-seronegative recipients. However, it remains unclear if allograft function is impacted by donor ...HCV-viremia or recipient HCV-serostatus.
We used national United States registry data to examine trends in HCV-viremic kidney use between 4/1/2015 and 3/31/2019. We applied advanced matching methods to compare eGFR for similar kidneys transplanted into highly similar recipients of kidney transplants.
Over time, HCV-seronegative recipients received a rising proportion of HCV-viremic kidneys. During the first quarter of 2019, 200 HCV-viremic kidneys were transplanted into HCV-seronegative recipients, versus 69 into HCV-seropositive recipients, while 105 HCV-viremic kidneys were discarded. The probability of HCV-viremic kidney discard has declined over time. Kidney transplant candidates willing to accept a HCV-seropositive kidney increased from 2936 to 16,809 from during this time period. When transplanted into HCV-seronegative recipients, HCV-viremic kidneys matched to HCV-non-viremic kidneys on predictors of organ quality, except HCV, had similar 1-year eGFR (66.3 versus 67.1 ml/min per 1.73 m
,
=0.86). This was despite the much worse kidney donor profile index scores assigned to the HCV-viremic kidneys. Recipient HCV-serostatus was not associated with a clinically meaningful difference in 1-year eGFR (66.5 versus 71.1 ml/min per 1.73 m
,
=0.056) after transplantation of HCV-viremic kidneys.
By 2019, HCV-seronegative patients received the majority of kidneys transplanted from HCV-viremic donors. Widely used organ quality scores underestimated the quality of HCV-viremic kidneys based on 1-year allograft function. Recipient HCV-serostatus was also not associated with worse short-term allograft function using HCV-viremic kidneys.
In response to recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the care of kidney transplant recipients (KTRs), the National Kidney Foundation's Kidney Disease ...Outcomes Quality Initiative (KDOQI) organized a working group of transplant nephrologists and surgeons to review these guidelines and comment on their relevance and applicability for US KTRs. The following commentaries on the KDIGO guidelines represent the consensus of our work group. The KDIGO transplant guidelines concentrated on aspects of transplant care most important to this population in the posttransplant period, such as immunosuppression, infection, malignancy, and cardiovascular care. Our KDOQI work group concurred with many of the KDIGO recommendations except in some important areas related to immunosuppression, in which decisions in the United States are largely made by transplant centers and are dependent in part on the specific patient population served. Most, but not all, KDIGO guidelines are relevant to US patients. However, implementation of many may remain a major challenge because of issues of limitation in resources needed to assist in the tasks of educating, counseling, and implementing and maintaining lifestyle changes. Although very few of the guidelines are based on evidence that is strong enough to justify their being used as the basis of policy or performance measures, they offer an excellent road map to navigate the complex care of KTRs.
The prevalence of hepatitis C virus infection is increased in patients with end stage kidney disease compared to the general population and is an adverse outcome determinant. Direct‐acting antiviral ...therapy for hepatitis C virus is changing the management paradigm of infected kidney transplant candidates and recipients, with potential to reduce patient morbidity and mortality. This review describes the hepatic and nonhepatic manifestations of hepatitis C virus in kidney transplant patients as well as management and treatment strategies to optimize transplant outcomes, highlighting the importance of direct‐acting antivirals in this population.
The advent of direct‐acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV‐infected donors. We conducted a single‐arm trial of ...orthotopic heart transplantation (OHT) from HCV‐infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40‐65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV‐genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt‐in for HCV nucleic‐acid‐test (NAT)+ donor offers to OHT was 39 days (interquartile range IQR 17‐57). The median donor age was 34 years (IQR 31‐37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR‐12). The 10th recipient had a positive cross‐match, experienced antibody‐mediated rejection and multi‐organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short‐term results suggest that HCV‐negative candidates transplanted with HCV‐infected hearts have acceptable outcomes.
The pilot USHER trial, involving 10 heart recipients, provides important evidence that transplanting hepatitis C virus–infected hearts into uninfected recipients poses reasonable risks and that hepatitis C cure rates are high even in the context of transplant immunosuppression.
Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) ...following deceased donor kidney transplantation. We report on the safety/efficacy of anti‐C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator‐sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19‐subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu‐treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant‐related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu‐treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180‐days post‐transplant, were also similar. Ecu administration was safe but did not reduce the rate of DGF in a high‐risk population of deceased donor recipients.
The results of two randomized controlled pilot trials show no efficacy for peritransplant administration of eculizumab in preventing delayed graft function following deceased donor kidney transplantation.
PURPOSE OF REVIEWWith improving short-term kidney transplant outcomes, recurrent glomerular disease is being increasingly recognized as an important cause of chronic allograft failure. Further ...understanding of the risks and pathogenesis of recurrent glomerular disease enable informed transplant decisions, along with the development of preventive and treatment strategies.
RECENT FINDINGSMultiple observational studies have highlighted differences in rates and outcomes for various recurrent glomerular diseases, although these rates have not markedly improved over the last decade. Emerging evidence supports use of rituximab to treat recurrent primary membranous nephropathy and possibly focal segmental glomerulosclerosis (FSGS), whereas eculizumab is effective in glomerular diseases associated with complement dysregulation C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS).
SUMMARYDespite the potential for recurrence in the allograft, transplant remains the optimal therapy for patients with advanced chronic kidney disease (CKD) secondary to primary glomerular disease. Biomarkers and therapeutic options necessitate accurate pretransplant diagnoses with opportunities for improved surveillance and treatment of recurrent glomerular disease posttransplant.
Right-Sizing Multiorgan Allocation Involving Kidneys Husain, S Ali; Hippen, Benjamin; Singh, Neeraj ...
Clinical journal of the American Society of Nephrology,
11/2023, Letnik:
18, Številka:
11
Journal Article
The prerequisite for an ‘undetectable’ HIV viral load has restricted access to transplantation for HIV–infected kidney recipients. However, HCV–infected recipients, owing to the historic limitations ...of HCV therapy in patients with renal disease, are commonly viremic at transplant and have universal access. To compare the effect of HIV, HCV, and HIV/HCV coinfection on kidney transplant patient and allograft outcomes, we performed a retrospective study of kidney recipients transplanted from January 1996 through December 2013. In multivariable analysis, patient (hazard ratio 0.90, 95% confidence interval 0.66–1.24) and allograft survival (0.60, 40–0.88) in 492 HIV patients did not differ significantly from the 117,791 patient-uninfected reference group. This was superior to outcomes in both the 5605 patient HCV group for death (1.44, 1.33–1.56) and graft loss (1.43, 1.31–1.56), as well as the 147 patient HIV/HCV coinfected group for death (2.26, 1.45–3.52) and graft loss (2.59, 1.60–4.19). HIV infection did not adversely affect recipient or allograft survival and was associated with superior outcomes compared with both HCV infection and HIV/HCV coinfection in this population. Thus, pretransplant viral eradication and/or immediate posttransplant eradication should be studied as potential strategies to improve posttransplant outcomes in HCV–infected kidney recipients.
In this issue, Alric and colleagues demonstrate through real-world experience that grazoprevir-elbasvir is safe and effective for treating hepatitis C in advanced kidney disease patients with higher ...comorbidity burdens. This commentary highlights that this and similar studies have primarily focused on treatment safety and efficacy, rather than the clinical impact of viral eradication. Critical knowledge gaps including which patients to treat, and when, as well as potential management strategies that may improve outcomes, are discussed.
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